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Purpose: Although ventilation/perfusion (V/Q) scintigraphy is a widely used imaging test, different options are possible for the acquisition and interpretation of the scan. The aim of this study was to assess current practices regarding the use and interpretation of lung scintigraphy in various clinical indications., Patients and Methods: An online survey comprising 25 questions was sent to nuclear medicine departments in Australia, Canada, France, Germany, and United States between 2022 and 2023. A single response per department was consolidated., Results: Four hundred nineteen responses were collected (Australia: 32, Canada: 58, France: 149, Germany: 92, and United States: 88). For acute pulmonary embolism (PE) diagnosis, 82.8% of centers reported using SPECT acquisitions (Australia: 93.3%, Canada: 91.8%, France: 99.2%, Germany: 96.2%, and United States: 32.1%). Among them, SPECT images were combined with a CT scan in 70.5% of centers. A total of 10.6% of centers reported not using ventilation for acute PE diagnosis. SPECT acquisition was used in 97.8% of centers using 99m Tc carbon particles, 97.1% 81m Kr gas, 58.7% 99m Tc-DTPA, and 19.4% 133 Xe gas, respectively. For V/Q SPECT interpretation, the EANM criteria were used in 65.0% of departments. A very wide variety of practices were observed in pregnant women and in COVID-19 patients. SPECT acquisition was widely used in the follow-up of PE and for the screening of chronic thromboembolic pulmonary hypertension (>90% of centers), with inconsistency regarding the interpretation of matched perfusion defects in this setting., Conclusions: This survey shows the strong adoption of SPECT in the various clinical indications of lung scintigraphy, except in the United States, where planar imaging is still mostly used. The survey also shows variability in interpretation criteria both for PE diagnosis and screening for chronic thromboembolic pulmonary hypertension, highlighting the need for further standardizations of practices., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Pulmonary embolism (PE) is a challenge to diagnose and when missed, exposes patients to potentially fatal recurrent events. Beyond CT pulmonary angiography (CTPA) and planar ventilation/perfusion (V/Q) scan, single photon emission CT (SPECT) V/Q emerged a new diagnostic modality of scintigraphic acquisition that has been reported to improve diagnostic performances. To date, no management outcome study or randomised trial evaluated an algorithm based on SPECT V/Q for PE diagnosis. We present the design of a randomised multicentre, international management study comparing SPECT V/Q with validated strategies., Material and Methods: We will include a total of 3672 patients with suspected PE requiring chest imaging, randomised into three different groups, each using a different diagnostic strategy based on SPECT V/Q, CTPA and planar V/Q scan. Randomisation will be unbalanced (2:1:1), with twice as many patients in SPECT V/Q arm (n=1836) as in CTPA and planar V/Q arms (n=918 in each). Our primary objective will be to determine whether a diagnostic strategy based on SPECT V/Q is non-inferior to previously validated strategies in terms of diagnostic exclusion safety as assessed by the 3-month risk of thromboembolism in patients with a negative diagnostic workup. Secondary outcomes will be the proportion of patients diagnosed with PE in each arm, patients requiring additional tests, the incidence of major and clinically relevant non-major bleeding and the incidence and cause of death in each arm., Ethics and Dissemination: This trial is funded by a grant from Brest University Hospital and by INVENT. The study protocol was approved by Biomedical Research Ethics Committee. The investigator or delegate will obtain signed informed consent from all patients prior to inclusion in the trial. Our results will inform future clinical practice guidelines and solve the current discrepancy between nuclear medicine guidelines and clinical scientific society guidelines., Trial Registration Number: NCT02983760., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The aim of this work was to compare anatomic and functional dose-volume parameters as predictors of acute radiation-induced lung toxicity (RILT) in patients with lung tumors treated with stereotactic body radiation therapy., Methods and Materials: Fifty-nine patients treated with stereotactic body radiation therapy were prospectively included. All patients underwent gallium 68 lung perfusion positron emission tomography (PET)/computed tomography (CT) imaging before treatment. Mean lung dose (MLD) and volumes receiving x Gy (VxGy, 5-30 Gy) were calculated in 5 lung volumes: the conventional anatomic volume (AV) delineated on CT images, 3 lung functional volumes (FVs) defined on lung perfusion PET imaging (FV50%, FV70%, and FV90%; ie, the minimal volume containing 50%, 70%, and 90% of the total activity within the AV), and a low FV (LFV; LFV = AV - FV90%). The primary endpoint of this analysis was grade ≥2 acute RILT at 3 months as assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Dose-volume parameters in patients with and without acute RILT were compared. Receiver operating characteristic curves assessing the ability of dose-volume parameters to discriminate between patients with and without acute RILT were generated, and area under the curve (AUC) values were calculated., Results: Of the 59 patients, 10 (17%) had grade ≥2 acute RILT. The MLD and the VxGy in the AV and LFV were not statistically different between patients with and without acute RILT (P > .05). All functional parameters were significantly higher in acute RILT patients (P < .05). AUC values (95% CI) for MLD AV, LFV, FV50%, FV70%, and FV90% were 0.66 (0.46-0.85), 0.60 (0.39-0.80), 0.77 (0.63-0.91), 0.77 (0.64-0.91), and 0.75 (0.58-0.91), respectively. AUC values for V20Gy AV, LFV, FV50%, FV70%, and FV90% were 0.65 (0.44-0.87), 0.64 (0.46-0.83), 0.82 (0.69-0.95), 0.81 (0.67-0.96), and 0.75 (0.57-0.94), respectively., Conclusions: The predictive value of PET perfusion-based functional parameters outperforms the standard CT-based dose-volume parameters for the risk of grade ≥2 acute RILT. Functional parameters could be useful for guiding radiation therapy planning and reducing the risk of acute RILT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this article the technique, interpretation, and diagnostic performance of scintigraphy for the diagnosis of acute pulmonary embolism (PE) are reviewed. Lung scintigraphy has stood the test of time as a reliable and validated examination for the determination of PE. Ventilation/perfusion (V/Q) lung scintigraphy assesses the functional consequences of the clot on its downstream vascular bed in conjunction with the underlying ventilatory status of the affected lung region, in contrast to CT pulmonary angiography (CTPA), which visualizes presence of the clot within affected vessels. Most-commonly used ventilation radiopharmaceuticals are Technetium-99m labeled aerosols (such as 99m Technetium-DTPA), or ultrafine particle suspensions ( 99m Tc-Technegas) which reach the distal lung in proportion to regional distribution of ventilation. Perfusion images are obtained after intravenous administration 99m Tc-labeled macro-aggregated albumin particles which lodge in the distal pulmonary capillaries. Both planar and tomographic methods of imaging, each favored in different geographical regions, will be described. Guidelines for interpretation of scintigraphy have been issues by both the Society of Nuclear Medicine and Molecular Imaging, and by the European Association of Nuclear Medicine. Breast tissue is particularly radiosensitive during pregnancy due to its highly proliferative state and many guidelines recommend use of lung scintigraphy rather than CTPA in this population. Several maneuvers are available in order to further reduce radiation exposure including reducing radiopharmaceutical dosages or omitting ventilation altogether, functionally converting the study to a low-dose screening examination; if perfusion defects are present, further testing is necessary. Several groups have also performed perfusion-only studies during the COVID epidemic in order to reduce risk of respiratory contagion. In patients where perfusion defects are present, further testing is again necessary to avoid false-positive results. Improved availability of personal protective equipment, and reduced risk of serious infection, have rendered this maneuver moot in most practices. First introduced 60 years ago, subsequent advances in radiopharmaceutical development and imaging methods have positioned lung scintigraphy to continue to play an important clinical and research role in the diagnosis of acute PE., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We aimed to assess the relationship between residual pulmonary vascular obstruction (RPVO) on planar lung scan after completion of at least 3 months of anticoagulant therapy for acute pulmonary embolism (PE) and the risk of recurrent venous thromboembolism (VTE) or death due to PE one year after treatment discontinuation. The systematic review was registered with the International Prospective Registry of Systematic Reviews (PROSPERO: CRD42017081080). The primary outcome measure was to generate a pooled estimate of the rate of recurrent VTE at one year in patient with RPVO diagnosed on planar lung scan after discontinuation of at least 3 months of anticoagulant treatment for an acute PE. Individual data were obtained for 809 patients. RPVO (ie, obstruction >0%) was found in 407 patients (50.3%) after a median of 6.6 months of anticoagulant therapy for a first acute PE. Recurrent VTE or death due to PE occurred in 114 patients (14.1%), for an annual risk of 6.4% (95% confidence interval, 4.7%-8.6%). Out of the 114 recurrent events, 63 occurred within one year after discontinuation of anticoagulant therapy corresponding to a risk of 8.1% (6.4%-9.8%) at 1 year. The risk of recurrent VTE at one year was 5.8% (4.4-7.2) in participants with RPVO <5%, vs 11.7% (9.5-13.8) in participants with RPVO ≥5%. RPVO is a significant predictor of the risk of recurrent venous thromboembolism. However, the risk of recurrent events remains too high in patients without residual perfusion defect for it to be used as a stand-alone test to decide on anticoagulation discontinuation., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Gallium-68 lung perfusion PET/CT is an emerging imaging modality for the assessment of regional lung function, especially to optimise radiotherapy (RT) planning. A key step of lung functional avoidance RT is the delineation of lung functional volumes (LFVs) to be integrated into radiation plans. However, there is currently no consistent and reproducible delineation method for LFVs. The aim of this study was to develop and evaluate an automated delineation threshold method based on total lung function for LFVs delineation with Gallium-68 MAA lung PET/CT imaging., Material and Method: Patients prospectively enrolled in the PEGASUS trial-a pilot study assessing the feasibility of lung functional avoidance using perfusion PET/CT imaging for lung stereotactic body radiotherapy (SBRT) of primary or secondary lesion-were analysed. Patients underwent lung perfusion MAA-68Ga PET/CT imaging and pulmonary function tests (PFTs) as part of pre-treatment evaluation. LFVs were delineated using two methods: the commonly used relative to the maximal pixel value threshold method (pmax threshold method, X%pmax volumes) and a new approach based on a relative to whole lung function threshold method (WLF threshold method, FVX% volumes) using a dedicated iterative algorithm. For both methods, LFVs were expressed in terms of % of the anatomical lung volume (AV) and of % of the total lung activity. Functional volumes were compared for patients with normal PFTs and pre-existing airway disease., Results: 60 patients were analysed. Among the 48 patients who had PFTs, 31 (65%) had pre-existing lung disease. The pmax and WLF threshold methods clearly provided different functional volumes with a wide range of relative lung function for a given pmax volume, and conversely, a wide range of corresponding pmax values for a given WLF volume. The WLF threshold method provided more reliable and consistent volumes with much lower dispersion of LFVs as compared to the pmax method, especially in patients with normal PFTs., Conclusions: We developed a relative to whole lung function threshold segmentation method to delineate lung functional volumes on perfusion PET/CT imaging. The automated algorithm allows for reproducible contouring. This new approach, relatively unaffected by the presence of hot spots, provides reliable and consistent functional volumes, and is clinically meaningful for clinicians.

Introduction: Prostate adenocarcinoma (CaP) is the leading cancer in men. After curative treatment, from 27% to 53% of patients will experience biochemical recurrence (BR). With the development of focal therapies, precise early identification of recurrence's sites is of utmost importance in order to deliver individualized treatment on positive lesions. The aim of this study was to assess the detection rate (DR) of 68 Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in selected patients with prostate cancer BR and recent negative 18 F-choline PET/CT., Patients and Methods: We performed a retrospective analysis including all patients with CaP referred for BR with a negative 18 F-choline PET/CT, and who underwent 68 Ga-PSMA-11 PET/CT between October, 2018 and December, 2019. The overall DR of 68 Ga-PSMA-11 PET/CT was calculated, and described according to BR characteristics especially PSA levels and velocity. Patients were followed up for at least 1 year. Patient management following 68 Ga-PSMA-11 PET/CT and PSA levels evolution after treatment were also recorded., Results: One hundred fifty-nine patients comprising 164 examinations were analyzed. The overall DR of 68 Ga-PSMA-11 PET/CT for BR was 65.9% (95CI, 58.6-73.1). The DR was 52.5% (95CI, 39.9-65.0), 70.6% (95CI, 55.3-85.9), 70.4% (95CI, 53.1-87.6), and 78.6% (95CI, 66.2-91.0) for PSA levels between 0.2 and 0.49 ng/mL, 0.5 to 0.99 ng/mL, 1 to 1.99 ng/mL and PSA ≥ 2 ng/mL, respectively. The DR was 70.7% (95CI, 59.0-82.4) with a PSA doubling time (PSA-DT) ≤6 months and 65.2% (95CI, 55.5-74.9) with a PSA-DT >6 months. Around 3/4 of patients (75.9%) with a positive 68 Ga-PSMA-11 PET/CT initiated treatment, including surgery (2.4%), stereotactic radiotherapy ± androgen deprivation therapy (ADT) (22%) or external conformational radiotherapy ± ADT (46.3%). Patient management changed in 43 cases (39.8%)., Conclusion: Our study confirmed the ability of 68 Ga-PSMA-11 PET/CT to detect occult biochemical recurrence, even in a selected population of CaP patients with negative 18 F-choline PET/CT, even at low PSA levels., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The aim of this study was to assess the feasibility of sparing functional lung areas by integration of pulmonary functional mapping guided by 68 Ga-perfusion PET/CT imaging in lung SBRT planification. Sixty patients that planned to receive SBRT for primary or secondary lung tumors were prospectively enrolled. Lung functional volumes were defined as the minimal volume containing 50% (FV50%), 70% (FV70%) and 90% (FV90%) of the total activity within the anatomical volume. All patients had a treatment planning carried out in 2 stages: an anatomical planning blinded to the PET results and then a functional planning respecting the standard constraints but also incorporating "lung functional volume" constraints. The mean lung dose (MLD) in functional volumes and the percentage of lung volumes receiving xGy (VxGy) within the lung functional volumes using both plans were calculated and compared. SBRT planning optimized to spare lung functional regions led to a significant reduction ( p < 0.0001) of the MLD and V5 to V20 Gy in all functional volumes. Median relative difference of the MLD in the FV50%, FV70% and FV90% was -8.0% (-43.0 to 1.2%), -7.1% (-34.3 to 1.2%) and -5.7% (-22.3 to 4.4%), respectively. Median relative differences for VxGy ranged from -12.5% to -9.2% in the FV50%, -11.3% to -7.2% in the FV70% and -8.0% to -5.3% in the FV90%. This study shows the feasibility of significantly decreasing the doses delivered to the lung functional volumes using 68 Ga-perfusion PET/CT while still respecting target volume coverage and doses to other organs at risk.

Lung stereotactic body radiotherapy (SBRT) is increasingly proposed, especially for patients with poor lung function who are not eligible for surgery. However, radiation-induced lung injury remains a significant treatment-related adverse event in these patients. Moreover, for patients with very severe COPD, we have very few data about the safety of SBRT for lung cancer. We present the case of a female with very severe chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in one second (FEV1) of 0.23 L (11%), for whom a localized lung tumor was found. Lung SBRT was the only possible treatment. It was allowed and safely performed, based on a pre-therapeutic evaluation of regional lung function with Gallium-68 perfusion lung positron emission tomography combined with computed tomography (PET/CT). This is the first case report to highlight the potential use of a Gallium-68 perfusion PET/CT in order to safely select patients with very severe COPD who can benefit from SBRT., Competing Interests: The authors declare no conflict of interest.

Abstract: Invented and first approved for clinical use in Australia 36 years ago, Technegas is the technology that enabled ventilation scintigraphy with 99m Tc-labeled carbon nanoparticles ( 99m Tc-CNP). The US Food and Drug Administration (FDA) has considered this technology for more than 30 years but only now is getting close to approving it. Meanwhile, more than 4.4 million patients benefited from this technology in 64 countries worldwide. The primary application of 99m Tc-CNP ventilation imaging is the diagnostic evaluation for suspicion of pulmonary embolism using ventilation-perfusion quotient (V/Q) imaging. Because of 99m Tc-CNP's long pulmonary residence, tomographic imaging emerged as the preferred V/Q methodology. The FDA-approved ventilation imaging agents are primarily suitable for planar imaging, which is less sensitive. After the FDA approval of Technegas, the US practice will likely shift to tomographic V/Q. The 99m Tc-CNP use is of particular interest in the COVID-19 pandemic because it offers an option of a dry radioaerosol that takes approximately only 3 to 5 tidal breaths, allowing the shortest exposure to and contact with possibly infected patients. Indeed, countries where 99m Tc-CNP was approved for clinical use continued using it throughout the COVID-19 pandemic without known negative viral transmission consequences. Conversely, the ventilation imaging was halted in most US facilities from the beginning of the pandemic. This review is intended to familiarize the US clinical nuclear medicine community with the basic science of 99m Tc-CNP ventilation imaging and its clinical applications, including common artifacts and interpretation criteria for tomographic V/Q imaging for pulmonary embolism., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication of a pulmonary embolism (PE) whose incidence and predictors are not precisely determined., Objective: To determine the frequency and predictors for CTEPH after a first unprovoked PE., Patients/methods: In a randomized trial comparing an additional 18-month warfarin versus placebo in patients after a first unprovoked PE initially treated with vitamin K antagonist for 6 months, we applied recommended CTEPH screening strategies through an 8-year follow-up to determine cumulative incidence of CTEPH. CTEPH predictors were estimated using Cox models. Pulmonary vascular obstruction (PVO) and systolic pulmonary arterial pressure (sPAP) at PE diagnosis and 6 months were studied by receiver operating curves analysis. All CTEPH cases and whether they were incident or prevalent were adjudicated., Results: During a median follow-up of 8.7 years, nine CTEPH cases were diagnosed among 371 patients, with a cumulative incidence of 2.8% (95% confidence interval [CI] 0.95-4.64), and of 1.31% (95% CI 0.01-2.60) after exclusion of five cases adjudicated as prevalent. At PE diagnosis, PVO > 45% and sPAP > 56 mmHg were associated with CTEPH with a hazard ratio (HR) of 33.00 (95% CI 1.64-667.00, p = .02) and 12.50 (95% CI 2.10-74.80, p < .01), respectively. Age > 65 years, lupus anticoagulant antibodies and non-O blood groups were also predictive of CTEPH. PVO > 14% and sPAP > 34 mmHg at 6 months were associated with CTEPH (HR 63.90 [95% CI 3.11-1310.00, p < .01]and HR 17.2 [95% CI 2.75-108, p < .01])., Conclusion: After a first unprovoked PE, CTEPH cumulative incidence was 2.8% during an 8-year follow-up. PVO and sPAP at PE diagnosis and at 6 months were the main predictors for CTEPH diagnosis., (© 2022 International Society on Thrombosis and Haemostasis.)

Introduction: Ventilation/Perfusion (V/Q) PET/CT is an emerging imaging modality for regional lung function evaluation. The same carrier molecules as conventional V/Q scintigraphy are used but they are radiolabelled with gallium-68 ( 68 Ga) instead of technetium-99m ( 99m Tc). A recurrent concern regarding V/Q PET imaging is the radiation dose to the healthcare workers. The aim of this study was to evaluate the total effective dose and the finger dose received by the technologist when performing a V/Q PET procedure, and to compare them with the radiations doses received with conventional V/Q scintigraphy, FDG PET and Ga DOTATOC PET procedures., Materials and Methods: The whole body dose measurement was performed 10 times for each of the evaluated procedures using an electronic personal dosimeter (ED). For V/Q PET and V/Q scintigraphy procedures, ventilation and perfusion stages were separately evaluated. Internal exposure was measured for ventilation procedures. Finger dose measurements were performed 5 times for each of the PET procedures using Thermoluminescence (TL) pellets., Results: The technologist effective dose when performing a V/Q PET procedure was 2.83 ± 0.67 μSv, as compared with 1.16 ± 0.34 μSv for conventional V/Q scintigraphy, 2.13 ± 0.77 μSv for [ 68 Ga]Ga-DOTATOC, and 2.86 ± 1.79 μSv for FDG PET procedures, respectively. The finger dose for the V/Q PET procedure was similar to the dose for a [ 68 Ga]Ga-DOTATOC scan (0.35 mSv and 0.32 mSv, respectively)., Conclusion: The technologist total effective dose for a V/Q PET procedure is ~2.4 higher than the dose for a conventional V/Q scintigraphy, but in the same range than the radiation exposure when performing common PET procedures, both in terms of total effective dose or finger dose. These results should be reassuring for the healthcare workers performing a V/Q PET procedure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Blanc-Béguin, Damien, Floch, Kerleguer, Hennebicq, Robin, Salaün and Le Roux.)

Introduction: Quantifying the pulmonary vascular obstruction index (PVOI) is essential for the management of patients with pulmonary embolism or chronic thromboembolic pulmonary hypertension (CTEPH). The reference method for quantifying the PVOI with planar lung ventilation/perfusion (V/Q) scintigraphy is the Meyer score, which was validated using pulmonary angiography as a reference standard. However, it is complex to use in daily practice. In contrast, a rapid and fast quantification method consists in estimating the PVOI based on the number of segmental perfusion defects. However, the accuracy of this method has never been evaluated. In this study, we aimed to compare PVOI quantification on planar V/Q scintigraphy assessed by a segmental visual scoring (SVS) to the Meyer score., Materials and Methods: The eligible study population consisted of consecutive patients who underwent planar V/Q scan for CTEPH screening. A central review was performed by three nuclear medicine physicians. PVOI was assessed by summing the number of segmental perfusion defects or equivalent (2 sub-segments = 1 segment = 5%) and by Meyer's method. The two interpretations were performed 6 months apart. A Spearman rank correlation coefficient was calculated to evaluate correlation between the two measurement methods. An intra-class correlation (ICC) was calculated to assess agreement. A Bland et Altman plot analysis was used to evaluate agreement between the two measurements., Results: A total of 226 V/Q scans were interpreted. Spearman rank correlation coefficient between SVS and Meyer was 0.963 (95%CI 0.952-0.971) for mismatched perfusion defects and 0.963 (95%CI 0.953-0.972) for perfusion defects regardless of ventilation. Intra-class correlation (ICC) for agreement was 0.978 (95%CI 0.972-0.983) for mismatched perfusion defects and 0.968 (95%CI 0.959-0.976) for perfusion defects regardless of ventilation. In Bland & Altmann analysis, the mean difference between the SVS method and the Meyer score was 0.42 and 0.61 for the mismatched or matched evaluation, respectively., Conclusion: Our study shows a high correlation, and low differences in PVOI quantification when using a segmental visual scoring (SVS) as compared to the Meyer score. The SVS has the great advantage to be easy and rapid to apply in daily practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Le Pennec, Tromeur, Orione, Robin, Le Mao, Gut-Gobert, Le Gal, Salaün and Le Roux.)

Purpose: In coronavirus disease 2019 (COVID-19) patients, clinical manifestations as well as chest CT lesions are variable. Lung scintigraphy allows to assess and compare the regional distribution of ventilation and perfusion throughout the lungs. Our main objective was to describe ventilation and perfusion injury by type of chest CT lesions of COVID-19 infection using V/Q SPECT/CT imaging., Patients and Methods: We explored a national registry including V/Q SPECT/CT performed during a proven acute SARS-CoV-2 infection. Chest CT findings of COVID-19 disease were classified in 3 elementary lesions: ground-glass opacities, crazy-paving (CP), and consolidation. For each type of chest CT lesions, a semiquantitative evaluation of ventilation and perfusion was visually performed using a 5-point scale score (0 = normal to 4 = absent function)., Results: V/Q SPECT/CT was performed in 145 patients recruited in 9 nuclear medicine departments. Parenchymal lesions were visible in 126 patients (86.9%). Ground-glass opacities were visible in 33 patients (22.8%) and were responsible for minimal perfusion impairment (perfusion score [mean ± SD], 0.9 ± 0.6) and moderate ventilation impairment (ventilation score, 1.7 ± 1); CP was visible in 43 patients (29.7%) and caused moderate perfusion impairment (2.1 ± 1.1) and moderate-to-severe ventilation impairment (2.5 ± 1.1); consolidation was visible in 89 patients (61.4%) and was associated with moderate perfusion impairment (2.1 ± 1) and severe ventilation impairment (3.0 ± 0.9)., Conclusions: In COVID-19 patients assessed with V/Q SPECT/CT, a large proportion demonstrated parenchymal lung lesions on CT, responsible for ventilation and perfusion injury. COVID-19-related pulmonary lesions were, in order of frequency and functional impairment, consolidations, CP, and ground-glass opacity, with typically a reverse mismatched or matched pattern., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Lung ventilation/perfusion (V/Q) positron emission tomography-computed tomography (PET/CT) is a promising imaging modality for regional lung function assessment. The same carrier molecules as a conventional V/Q scan (i.e., carbon nanoparticles for ventilation and macro aggregated albumin particles for perfusion) are used, but they are labeled with gallium-68 ( 68 Ga) instead of technetium-99m ( 99m Tc). For both radiopharmaceuticals, various production processes have been proposed. This article discusses the challenges associated with the transition from 99m Tc- to 68 Ga-labelled radiopharmaceuticals. The various production and optimization processes for both radiopharmaceuticals are reviewed and discussed for optimal clinical use.

Pulmonary functional imaging has demonstrated potential to improve thoracic radiotherapy. The purpose of this study was twofold: 1) to quantify ventilation/perfusion relationships in lung cancer patients using a new functional imaging approach, gallium-68 ( 68 Ga)-positron emission tomography/computed tomography (PET/CT); and 2) to compare ventilation/perfusion matching with diffusing capacity of the lung for carbon monoxide (D LCO ). Voxel-wise correlations between ventilation and perfusion varied widely among 19 patients (range: 0.26-0.88). 68 Ga-PET/CT-measured percent gas exchanging lung volume was moderately correlated with D LCO (≤0.59). Our findings suggested that 68 Ga-PET/CT ventilation/perfusion imaging provided complementary information and a reasonable surrogate for gas exchange in lung cancer patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is a major challenge as it is a curable cause of pulmonary hypertension (PH). Ventilation/Perfusion (V/Q) lung scintigraphy is the imaging modality of choice for the screening of CTEPH. However, there is no consensus on the criteria to use for interpretation. The aim of this study was to assess the accuracy of various interpretation criteria of planar V/Q scintigraphy for the screening of CTEPH in patients with PH., Methods: The eligible study population consisted of consecutive patients with newly diagnosed PH in the Brest University Hospital, France. Final diagnosis (CTEPH or non-CTEPH) was established in a referential center on the management of PH, based on the ESC/ERS guidelines and a minimum follow-up of 3 years. A retrospective central review of planar V/Q scintigraphy was performed by three nuclear physicians blinded to clinical findings and to final diagnosis. The number, extent (sub-segmental or segmental) and type (matched or mismatched) of perfusion defects were reported. Sensitivity and specificity were evaluated for various criteria based on the number of mismatched perfusion defects and the number of perfusion defects (regardless of ventilation). Receiver operating characteristic (ROC) curves were generated and areas under the curve (AUC) were calculated for both., Results: A total of 226 patients with newly diagnosed PH were analyzed. Fifty six (24.8%) were diagnosed with CTEPH while 170 patients (75.2%) were diagnosed with non-CTEPH. The optimal threshold was 2.5 segmental mismatched perfusion defects, providing a sensitivity of 100 % (95% CI 93.6-100%) and a specificity of 94.7% (95%CI 90.3-97.2%). Lower diagnostic cut-offs of mismatched perfusion defects provided similar sensitivity but lower specificity. Ninety five percent of patients with CTEPH had more than 4 segmental mismatched defects. An interpretation only based on perfusion provided similar sensitivity but a specificity of 81.8% (95%CI 75.3-86.9%)., Conclusion: Our study confirmed the high diagnostic performance of planar V/Q scintigraphy for the screening of CTEPH in patients with PH. The optimal diagnostic cut-off for interpretation was 2.5 segmental mismatched perfusion defects. An interpretation only based on perfusion defects provided similar sensitivity but lower specificity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Le Pennec, Tromeur, Orione, Robin, Le Mao, De Moreuil, Jevnikar, Hoffman, Savale, Couturaud, Sitbon, Montani, Jaïs, Le Gal, Salaün, Humbert and Le Roux.)

Background: Advanced age is an independent poor prognostic factor of diffuse large B-cell lymphoma (DLBCL). PMitCEBO (mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone) is an alternative to the cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen to decrease side effects in elderly patients. Many studies have shown prognostic value of an interim FDG PET-CT to predict survival. A recent consensus (ICML, Lugano 2013) has suggested using the 5-point scale Deauville criteria instead of those of the International Harmonization Project (IHP) to visually assess the response on interim PET. The objective of this study was to evaluate the prognostic value of an interim FDG PET-CT in patients older than 60 with treated DLBCL and to compare IHP and 5-PS Deauville visual interpretation to predict survival., Methods: Forty-eight patients (mean age 73.2±5.2 years) treated by R-PMitCEBO for DLBCL undergoing FDG PET-CT before and after 3 cycles of treatment were retrospectively included. Event-free survival and overall survival were determined by Kaplan-Meier method and compared with interim PET-CT results using IHP and 5-PS Deauville criteria., Results: Interim PET results using 5-PS Deauville criteria were significantly correlated with EFS (P<0.0001) and OS (P=0.001) whereas they were moderately correlated with EFS (P=0.046) and not with OS (P=0.106) using IHP criteria. Two-year EFS and OS rates were 86.5% and 89.2%, respectively, for patients in 1-3 score group, and 27.3% and 36.4%, respectively, for patients in ≥4 score group using the Deauville criteria., Conclusions: Our results confirmed the prognostic value of an interim PET-CT in elderly patients with DLBCL and the better performance of the 5-PS Deauville criteria.

Lung PET/CT is a promising imaging modality for regional lung function assessment. Our aim was to develop and validate a fast, simple, and fully automated GMP compliant [ 68 Ga]Ga-MAA labeling procedure, using a commercially available [ 99m Tc]Tc-MAA kit, a direct gallium-68 eluate and including a purification of the [ 68 Ga]Ga-MAA. Method: The synthesis parameters (pH, heating temperature) were manually determined. Automated 68 Ga-labeling of MAA was then developed on a miniAIO (Trasis®, Ans, Belgium) module. An innovative automated process was developed for the purification. The process was then optimized and adapted to automate both the [ 68 Ga]Ga-MAA synthesis and the isolation of gallium-68 eluate required for the pulmonary ventilation PET/CT. Results: The 15-min process demonstrated high reliability and reproducibility, with high synthesis yield (>95 %). Mean [ 68 Ga]Ga-MAA radiochemical purity was 99 % ± 0.6 %. The 68 Ga-labeled MAA particles size and morphology remained unchanged. Conclusion: A fast, user friendly, and fully automated process to produce GMP [ 68 Ga]Ga-MAA for clinical use was developed. This automated process combining the advantages of using a non-modified MAA commercial kit, a gallium-68 eluate without pre-purification and an efficient final purification of the [ 68 Ga]Ga-MAA may facilitate the implementation of lung PET/CT imaging in nuclear medicine departments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Blanc-Béguin, Masset, Robin, Tripier, Hennebicq, Guilloux, Vriamont, Warnier, Cogulet, Eu, Salaün and Le Roux.)

Despite the introduction of new radiotherapy techniques, such as intensity modulated radiation therapy or stereotactic body radiation therapy, radiation induced lung injury remains a significant treatment related adverse event of thoracic radiation therapy. Functional lung avoidance radiation therapy is an emerging concept in the treatment of lung disease to better preserve lung function and to reduce pulmonary toxicity. While conventional ventilation/perfusion (V/Q) lung scintigraphy is limited by a relatively low spatial and temporal resolution, the recent advent of 68 Gallium V/Q lung PET/CT imaging offers a potential to increase the accuracy of lung functional mapping and to better tailor lung radiation therapy plans to the individual's lung function. Lung PET/CT imaging may also improve our understanding of radiation induced lung injury compared to the current anatomical based dose-volume constraints. In this review, recent advances in radiation therapy for the management of primary and secondary lung tumors and in V/Q PET/CT imaging for the assessment of functional lung volumes are reviewed. The new opportunities and challenges arising from the integration of V/Q PET/CT imaging in radiation therapy planning are also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lucia, Rehn, Blanc-Béguin and Le Roux.)

Background: In patients with pulmonary embolism (PE), there is a growing interest in quantifying the pulmonary vascular obtruction index (PVOI), which may be an independent risk factor for PE recurrence. Perfusion SPECT/CT is a very attractive tool to provide an accurate quantification of the PVOI. However, there is currently no reliable method to automatically delineate and quantify it. The aim of this phantom study was to assess and compare 3 segmentation methods for PVOI quantification with perfusion SPECT/CT imaging., Methods: Three hundred ninety-six SPECT/CT scans, with various PE scenarios (n = 44), anterior to posterior perfusion gradients (n = 3), and lung volumes (n = 3) were simulated using Simind software. Three segmentation methods were assesssed: (1) using an intensity threshold expressed as a percentage of the maximal voxel value (MaxTh), (2) using a Z-score threshold (ZTh) after building a Z-score parametric lung map, and (3) using a relative difference threshold (RelDiffTh) after building a relative difference parametric map. Ninety randomly selected simulations were used to define the optimal threshold, and 306 simulations were used for the complete analysis. Spacial correlation between PE volumes from the phantom data and the delineated PE volumes was assessed by computing DICE PE indices. Bland-Altman statistics were used to calculate agreement for PVOI between the phantom data and the segmentation methods., Results: Mean DICE PE index was higher with the RelDiffTh method (0.85 ± 0.08), as compared with the MaxTh method (0.78 ± 0.16) and the ZTh method (0.67 ± 0.15). Using the RelDiffTh method, mean DICE PE index remained high (> 0.81) regardless of the perfusion gradient and the lung volumes. Using the RelDiffTh method, mean relative difference in PVOI was - 12%, and the limits of agreement were - 40% to 16%. Values were 3% (- 75% to 81%) for MaxTh method and 0% (- 120% to 120%) for ZTh method. Graphycal analysis of the Bland-Altman graph for the RelDiffTh method showed very close estimation of the PVOI for small and medium PE, and a trend toward an underestimation of large PE., Conclusion: In this phantom study, a delineation method based on a relative difference parametric map provided a good estimation of the PVOI, regardless of the extent of PE, the intensity of the anterior to posterior gradient, and the whole lung volumes.

Background:  We aimed to assess whether high pulmonary vascular obstruction index (PVOI) measured at the time of pulmonary embolism (PE) diagnosis is associated with an increased risk of recurrent venous thromboembolism (VTE)., Study Design and Methods:  French prospective cohort of patients with a symptomatic episode of PE diagnosed with spiral computerized tomography pulmonary angiography (CTPA) or ventilation-perfusion (V/Q) lung scan and a follow-up of at least 6 months after anticoagulation discontinuation. PVOI was assessed based on the available diagnostic exam (V/Q lung scan or CTPA). All patients had standardized follow-up and independent clinicians adjudicated all deaths and recurrent VTE events. Main outcome was recurrent VTE after stopping anticoagulation., Results:  A total of 418 patients with PE were included. During a median follow-up period of 3.6 (1.2-6.0) years, 109 recurrences occurred. In multivariate analysis, PVOI ≥ 40% was an independent risk factor for recurrence (hazard ratio 1.77, 95% confidence interval 1.20-2.62, p  < 0.01), whether PE was provoked by a major transient risk factor or not. A threshold at 41% was identified as the best value associated with the risk of recurrence 6 months after stopping anticoagulation (area under curve = 0.64)., Conclusion:  PVOI ≥ 40% at PE diagnosis was an independent risk factor for recurrence VTE. Further prospective validation studies are needed., Competing Interests: F.C. reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Daiichi Sankyo, Leo Pharma, Intermune, and Actelion. C.O. declares he has no conflict of interest related to this research. C.T. declares she has no conflict of interest related to this research. P.R. declares he has no conflict of interest related to this research. R.L.M. declares he has no conflict of interest related to this research. P.-Y.L.R. declares he has no conflict of interest related to this research. P.-Y.S. declares he has no conflict of interest related to this research. C.H. declares he has no conflict of interest related to this research. L.B. declares he has no conflict of interest related to this research. P.-Y.L.F. declares he has no conflict of interest related to this research. M.N. declares he has no conflict of interest related to this research. M.G. declares she has no conflict of interest related to this research. E.P. declares she has no conflict of interest related to this research. C.A.L. declares she has no conflict of interest related to this research. K.L. reports having received personal fees from Bayer-Health Care, Bristol-Myers Squibb, and Boehringer Ingelheim. C.L. reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Daiichi Sankyo, Leo Pharma, Intermune, and Actelion. No other potential conflict of interest relevant to this article was reported., (Thieme. All rights reserved.)

Purpose: The aim of this study was to assess image quality and lesion detectability acquired with a digital Positron Emission Tomography/Computed Tomography (PET/CT) Siemens Biograph Vision 600 system. Material and Methods: Consecutive patients who underwent a FDG PET/CT during the first week of use of a digital PET/CT (Siemens Biograph Vision 600) at the nuclear medicine department of the university hospital of Brest were analyzed. PET were realized using list mode acquisition. For all patients, 4 datasets were reconstructed. We determined, according to phantom measurements, an equivalent time acquisition/reconstruction parameters pair of the digital PET/CT corresponding to an analog PET/CT image quality ("analog-like") as reference dataset. We compared the reference dataset with 3 others digital PET/CT reconstruction parameters, allowing a decrease of emission duration: 60, 90, and 120 s per bed position. Three nuclear medicine physicians evaluated independently, for each dataset, overall image quality [Maximal Intensity Projection (MIP), noise, sharpness] using a 4-point scale. Physicians assessed also lesion detection capability by reporting new visible lesions on each digital datasets with their confidence level in comparison with analog-like dataset. Results: Ninety-eight patients were analyzed. Image quality of MIP (IQ MIP ), sharpness (IQ SHARPNESS ), and noise (IQ NOISE ) of all digital datasets (60, 90, and 120 s) were better than those evaluated with analog-like reconstruction. Moreover, digital PET/CT system improved IQ MIP , IQ NOISE , and IQ SHARPNESS whatever the BMI. Lesion detection capability and confidence level were higher for 60, 90, 120 s per bed position, respectively, than for analog-like images. Conclusion: Our study demonstrated an improvement of image quality and lesion detectability with a digital PET/CT system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Delcroix, Bourhis, Keromnes, Robin, Le Roux, Abgral, Salaun and Querellou.)

Objectives: 68 Ga Ventilation/Perfusion V/Q PET-CT is a promising imaging tool for pulmonary embolism diagnosis. However, no study has verified whether the interpretation is reproducible between different observers. The aim of this study was to assess the interobserver agreement in the interpretation of V/Q PET-CT for the diagnosis of acute PE, and to compare it to the interobserver agreement of CTPA interpretation. Methods: Twenty-four cancer patients with suspected acute PE underwent V/Q PET-CT and CTPA within 24 h as part of a prospective pilot study evaluating V/Q PET-CT for the management of patients with suspected PE. V/Q PET-CT and CTPA scans were reassessed independently by four nuclear medicine physicians and four radiologists, respectively. Physicians had different levels of expertise in reading V/Q scintigraphy and CTPA. Interpretation was blinded to the initial interpretation and any clinical information or imaging test result. For each modality, results were reported on a binary fashion. V/Q PET/CT scans were read as positive if there was at least one segmental or two subsegmental mismatched perfusion defects. CTPA scans were interpreted as positive if there was a constant intraluminal filling defect. Interobserver agreement was assessed by calculating kappa (κ) coefficients. Results: Out of the 24 V/Q PET-CT scans, the diagnostic conclusion was concordantly negative in 22 patients and concordantly positive in one patient. The remaining scan was interpreted as positive by one reader and negative by three readers. Out of the 24 CTPA scans, the diagnostic conclusion was concordantly negative in 16 and concordantly positive in one. Out of the seven remaining scans, PE was reported by one reader in four cases, by two readers in two cases, by three readers in one case. Most of discordant results on CTPA were related to clots reported on subsegmental arteries. Mean kappa coefficient was 0.79 for V/Q PET-CT interpretation and 0.39 for CTPA interpretation. Conclusions: Interobserver agreement in the interpretation of V/Q PET-CT for PE diagnosis was substantial (kappa 0.79) in a population with a low prevalence of significant PE. Agreement was lower with CTPA, mainly as a result of discrepancies at the level of the subsegmental arteries., Competing Interests: Unrelated to this study, MH reports grant funding from the Prostate Cancer Foundation,Movember, Prostate Cancer Foundation of Australia, Medical Research Future Fund (MRFF), Victorian Cancer Agency and the U.S. Department of Defence. He has received honorarium for educational lectures or travel from Janssen, Sanofi Genzyme and Ipsen. MH has received industry grant funding from Endocyte (now a Novartis company). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Le Pennec, Iravani, Woon, Dissaux, Gest, Le Floch, Salaün, Le Gal, Hofman, Hicks and Le Roux.)

Purpose: The use of 68 Ga-labelled carbon nanoparticles has been proposed for lung ventilation PET/CT imaging. However, no study has assessed the physical properties of 68 Ga-labelled carbon nanoparticles. The aim of this study therefore was to evaluate the shape and size of 68 Ga-labelled carbon nanoparticles, and to determine the composition of the aerosol, as opposed to 99m Tc-labelled carbon nanoparticles aerosol., Procedures: 99m Tc- and 68 Ga-labelled carbon nanoparticles, stable gallium carbon nanoparticles, 0.9 % NaCl and 0.1 N HCl-based carbon nanoparticles were produced using an unmodified Technegas® generator, following the usual technique used for clinical Technegas® production. The shape and size of particles were studied by transmission electron microscopy (TEM) after decay of the radioactive samples. The composition of the 68 Zn- and 99 Tc-labelled carbon nanoparticles aerosols was assessed using scanning electron microscopy (SEM) coupled with energy dispersive X-ray (EDX) analysis after decay of the 68 Ga- and 99m Tc-labelled carbon nanoparticles, respectively., Results: On TEM, all samples showed similar shape with hexagonally structured primary particles, agglomerated in clusters. The mean diameters of primary stable gallium carbon nanoparticles, 99 Tc- and 68 Zn-labelled carbon nanoparticles were 22.4 ± 10 nm, 20.9 ± 7.2 nm and 19.8 ± 11.7 nm, respectively., Conclusion: Using Technegas® generator in the usual clinical way, 99m Tc- and 68 Ga-labelled carbon nanoparticles demonstrated similar shape and diameters in the same size range size. These results support the use of 68 Ga-labelled carbon nanoparticles for the assessment of regional lung ventilation function with PET imaging.

Background: Ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) has largely replaced conventional planar V/Q scan in nuclear medicine departments for pulmonary embolism (PE) diagnosis. However, the diagnostic performance of the test and its role in the diagnostic management of acute PE are still a matter of debate., Objective: The primary aim was to establish the diagnostic accuracy (sensitivity, specificity) of V/Q SPECT for PE diagnosis. The secondary aim was to review the clinical outcomes of patients investigated for PE suspicion with a standardized algorithm based on V/Q SPECT., Methods: We conducted a systematic review of diagnostic accuracy and management outcome studies involving patients evaluated with V/Q SPECT for suspected acute PE. We searched from inception to June 23, 2020, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for diagnostic accuracy studies, randomized controlled trials, and observational cohort studies. The methodological quality and risk of bias of eligible studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and the Risk of Bias in Nonrandomized Studies of Interventions tools., Results: We identified 13 accuracy studies and one prospective outcome study. Eleven diagnostic accuracy studies were deemed at high risk of bias in at least two of the four domains of QUADAS-2 evaluation and a further two studies raised concerns regarding the applicability of results, precluding the meta-analysis for accuracy indices. The only prospective cohort study demonstrated critical risk of bias., Conclusions: Although V/Q SPECT has been widely implemented in daily clinical practice, the exact diagnostic performance of V/Q SPECT for PE is still unknown. This systematic review clearly identifies knowledge gaps and sets the agenda for future research., (© 2020 International Society on Thrombosis and Haemostasis.)

Background: We aimed to determine the prevalence of residual pulmonary vascular obstruction (RPVO) after symptomatic pulmonary embolism (PE) and to identify risk factors for RPVO., Methods: On the basis of a prospective cohort of patients with a documented symptomatic venous thromboembolism, we included patients who had an acute PE and underwent a ventilation/perfusion lung scan at 3 to 24 months during the follow-up after PE. RPVO score was assessed for each patient. Initial pulmonary vascular obstruction at PE diagnosis was also assessed when available. Univariable and multivariable analyses were performed with preselected data to identify predictors for persistent defect defined as RPVO ≥ 5%., Results: Among the 537 included patients, 278 (51.8%) had RPVO ≥ 5%, and 191 (35.6%) had RPVO ≥ 10%. In primary multivariate analysis on overall population, age ≥ 65 years (odds ratio [OR] 2.25, 95% CI, 1.45-3.52) and chronic respiratory failure (OR 3.19, 95% CI, 1.22-10.04) were independent predictors of RPVO ≥ 5%. In secondary multivariate analysis restricted to 256 patients with available initial pulmonary vascular obstruction score at index PE (IPVO), age ≥ 65 years (OR 2.78, 95% CI, 1.41-5.53), unprovoked PE (OR 2.11, 95% CI, 1.11-4.07) and IPVO ≥ 20% (OR 2.94, 95% CI, 1.68-5.20) were found to be independent risk factors for RVPO ≥5%., Conclusion: In this selected population of patients with an acute PE, age ≥ 65 years, unprovoked PE and IPVO ≥ 20% at PE diagnosis appeared to be risk factors for residual pulmonary vascular obstruction measured at three to 24 months., Competing Interests: Declaration of competing interest All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Picart declares he has no conflict of interest related to this research. Dr. Robin declares he has no conflict of interest related to this research. Dr. Tromeur declares she has no conflict of interest related to this research. Dr. Orione declares he has no conflict of interest related to this research. Ms. Raj declares she has no conflict of interest related to this research. Dr. Ferrieres declares he has no conflict of interest related to this research. Dr. Le Mao declares he has no conflict of interest related to this research. Dr. Le Roux declares he has no conflict of interest related to this research. Dr. Le Floch declares he has no conflict of interest related to this research. Ms. Lemarie declares she has no conflict of interest related to this research. Dr. Nonent declares he has no conflict of interest related to this research. Ms. Guegan declares she has no conflict of interest related to this research. Dr. Le Roux declares he has no conflict of interest related to this research. Dr. Leroyer reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Daiichi Sankyo, Leo Pharma, Intermune and Actelion. Dr. Lacut reports having received personal fees from Bayer-Health Care, Bristol-Myers Squibb and Boehringer Ingelheim. Dr. Salaun declares he has no conflict of interest related to this research. Dr. Couturaud reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer and Astra Zeneca and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Boehringer Ingelheim, Leo Pharma, Intermune and Actelion. No other potential conflict of interest relevant to this article was reported., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Venous thromboembolism (VTE) may be the first manifestation of cancer. We aimed at evaluating the performance of 18 F-Fluorodesoxyglucose Positron-Emission Tomography/Computed Tomography (FDG PET/CT) for occult cancer screening in patients with unprovoked VTE., Methods: This was a pre-specified analysis of a systematic review and individual patient data meta-analysis including prospective studies assessing cancer screening in patients with unprovoked VTE. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG PET/CT were calculated based on cancer diagnosis during a 1-year follow-up period., Results: Four studies were identified as using FDG PET/CT as part of their extensive screening strategy. Out of the 332 patients who underwent FDG PET/CT, the scan was interpreted as positive in 67 (20.2%), as equivocal in 27 (8.1%), and as negative in 238 (71.7%). Seventeen (5.1%) patients were diagnosed with cancer at inclusion or during the 12-month follow up period. All cancers were diagnosed at initial screening. Pooled sensitivity, specificity, NPV, and PPV were 87.3% (95% CI, 55.3 to 97.4), 70.2% (95% CI, 48.2 to 85.6), 98.9% (95% CI, 94.3 to 99.7), and 17.9% (95% CI, 8.5 to 33.6), respectively., Conclusion: FDG PET/CT appears to have satisfactory accuracy indices for cancer diagnosis in patients with unprovoked VTE. In particular, it exhibits a very high negative predictive value and could be used to rule out the presence of an underlying occult malignancy in this setting., Competing Interests: Declaration of competing interest Dr. Le Gal holds an Early Researcher Award from the Province of Ontario; a Heart and Stroke Foundation of Canada (HSFC) Ontario Mid-Career Investigator Award; and the Chair on Diagnosis of Venous Thromboembolism from the Department of Medicine at the University of Ottawa. Dr. Salaun reports a grant from the French Health Ministry (PHRC Cancer 2008) during the conduct of the MVTEP study. Authors not named here have disclosed no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To assess the diagnostic accuracy of iodine map computed tomography pulmonary angiography (CTPA), for segment-based evaluation of lung perfusion in patients with acute pulmonary embolism (PE), using perfusion single-photon emission CT (SPECT) imaging as a reference standard., Methods: Thirty participants who have been diagnosed with acute pulmonary embolism on CTPA underwent perfusion SPECT/CT within 24 h. Perfusion SPECT and iodine map were independently interpreted by 2 nuclear medicine physicians and 2 radiologists. For both modalities, each segment was classified as normoperfused or hypoperfused, as defined by a perfusion defect of more than 25% of a segment. The primary end point was the diagnostic accuracy (sensitivity and specificity) of iodine map for segment-based evaluation of lung perfusion, using perfusion SPECT imaging as a reference standard. Following blinded interpretation, a retrospective explanatory analysis was performed to determine potential causes of misinterpretation., Results: The median time between CTPA with iodine maps and perfusion SPECT was 14 h (range 2-23 h). A total of 597 segments were analyzed. Sensitivity and specificity of iodine maps with CTPA for the detection of segmental perfusion defects were 231/284 = 81.3% (95% CI 76.4 to 85.4%) and 247/313 = 78.9% (95% CI 74.1 to 83.1%), respectively. In retrospect, false results were explained in 48.7%., Conclusion: Iodine map CTPA showed promising results for the assessment of pulmonary perfusion in patients with acute PE, with sensitivity of 81.3% and specificity of 78.9%, respectively. Recognition of typical pitfalls such as atelectasis, fissures, or beam-hardening artifacts may further improve the accuracy of the test., Key Points: • Sensitivity and specificity of iodine subtraction maps for the detection of segmental perfusion defects were 81.3% (95% CI 76.4 to 85.4%) and 78.9% (95% CI 74.1 to 83.1%), respectively. • Recognition of typical pitfalls such as atelectasis, fissures, or beam-hardening artifacts may further improve the diagnostic accuracy of the test.

Background: There is currently no reliable or validated tool to delineate and quantify functional lung volumes with ventilation/perfusion (V/Q) SPECT/CT. The main challenges encountered include the physiological non-uniformity of lung function, such as the anterior-to-posterior gradient on perfusion images, and the lack of ground truth to assess the accuracy of delineation algorithms. In that respect, Monte-Carlo simulations would be an interesting tool. Thus, the aim of this study was to develop a realistic model of dual-isotope lung V/Q SPECT-CT Monte-Carlo simulations, integrating the anterior to posterior gradient on perfusion. Methods: Acquisitions and simulations parameters were set in accordance to nuclear medicine guidelines for V/Q lung SPECT-CT. Projections were acquired and simulated, then the reconstructions [with and without attenuation correction (AC)] were compared. A model was built from a patient's CT scan. To model the anterior to posterior gradient, the lungs were divided into sixteen coronal planes, where a rising radioactivity concentration was set. To assess the realism of simulations, they were compared to a normal co-registered normal cases database in terms of pixelwize Z-score map. Results: For ventilation images, mean (SD) Zscores on Zscore maps were -0.2 (0.7) and -0.2 (0.7) for AC and noAC images, respectively. For perfusion images, mean (SD) Zscores were -0.2 (0.6) and -0.1 (0.6) for AC and noAC images, respectively. Conclusion: We developed a model for dual isotopes lung V/Q SPECT-CT, integrating the anterior-to-posterior gradient on perfusion images. This model could be used to build a catalog of clinical scenarios, in order to test delineation methods of functional lung volumes., (Copyright © 2020 Bourhis, Wagner, Essayan, Robin, Le Pennec, Salaun and Le Roux.)

Background: We aimed to validate the Men Continue and HERDOO2 (HERDOO2), D-dimer, age, sex, hormonal therapy (DASH), and updated Vienna recurrent venous thromboembolism prediction models in a population composed entirely of first unprovoked pulmonary embolism, and to analyze the impact of the addition of the pulmonary vascular obstruction index (PVOI) on score accuracy., Methods: Analyses were based on the double-blind, randomized PADIS-PE trial, which included 371 unprovoked pulmonary embolism patients initially treated for 6 months, successively randomized to receive an additional 18 months of warfarin or placebo, and subsequently followed-up for 2 years., Results: The HERDOO2, DASH, and updated Vienna scores displayed C-statistics of 0.61 (95% CI 0.54-0.68), 0.60 (95% CI 0.53-0.66), and 0.58 (95% CI 0.51-0.66), respectively. Only the HERDOO2 score identified low recurrence risk patients (<3%/year) after anticoagulation was stopped. When added to either of the prediction models, PVOI measured at pulmonary embolism diagnosis, after 6 months of anticoagulation, or both, improved scores' C-statistics between +0.06 and +0.11 points and consistently led to identifying at least 50% of patients who experienced recurrence but in whom the scores would have indicated against extended anticoagulation., Conclusions: In patients with a first unprovoked pulmonary embolism, the HERDOO2 score is able to identify patients with a low recurrence risk after treatment discontinuation. Addition of PVOI improves accuracy of all scores., Clinical Trials Registration: URL: http://www.controlled-trials.com. Unique identifier: NCT00740883., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Emphysema severity is frequently measured on CT via densitometry. Correlation with scintigraphic and spirometric functional measures of ventilation or perfusion varies widely, and no prior study has evaluated correlation between densitometry and lobar ventilation/perfusion in patients with severe emphysema. The aim of this study was to evaluate the utility and findings of gallium-68 ( 68 Ga) ventilation/perfusion positron emission tomography-CT ( 68 Ga-VQ/PET-CT) in severe emphysema assessment., Methods: Fourteen consecutive patients undergoing evaluation for bronchoscopic lung volume reduction between March 2015 and March 2018 underwent 68 Ga-VQ/PET-CT assessment for lobar functional lung mapping, in addition to CT densitometry. Correlations between CT densitometry and 68 Ga-VQ/PET-CT parameters for individual lobar lung function were sought., Results: CT densitometry assessment of emphysema correlated only weakly (R 2 = 0.13) with lobar perfusion and was not correlated with ventilation (R 2 = 0.04). Densitometry was moderately (R 2 = 0.67) correlated with V/Q units in upper lobes, though poorly reflected physiological function in lower lobes (R 2 = 0.19). Emphysema severity, as measured by CT densitometry, was moderately correlated with proportion of normal V/Q units and matched V/Q defects in individual lobes., Conclusions: Assessment of lobar pulmonary function by 68 Ga-VQ/PET-CT provides physiologic information not evident on CT densitometry such as ventilation and perfusion specifics and matched defects. Further research is needed to see if the discordant findings on 68 Ga-VQ/PET-CT provide prognostic information or can be used to modify patient management and improve outcomes.

Background: Food consumption, sleep duration and overweight were assessed in rural and urban Melanesian adolescents., Methods: A cross-sectional survey of 312 rural and 104 urban adolescents (11-16 years old) was conducted. Food intakes were assessed by a 26-item food frequency questionnaire and then categorised into the number of serves from each of the three recommended Pacific food groups (energy foods, protective foods, bodybuilding foods), with two additional categories for foods and drinks to be avoided i.e., processed foods and sugary drinks. Number of food serves were compared with the guidelines of 50% serves from energy foods, 35% serves from protective foods and 15% serves from bodybuilding foods. Sleep duration as hours per day was self-reported and body mass index (BMI) was calculated from measured weight and height., Results: Approximately 17.9% of rural and 26.9% of urban adolescents met the guidelines for energy foods; 61.5% rural and 69.2% urban met the serves for protective foods and 88.5% and 94.2% met the serves for bodybuilding foods. Less than 6.4% rural and 1.9% urban adolescents avoided processed foods but 61.5% rural and 56.7% urban avoided sugary beverages. Sleep duration for school days was below the international recommendations and did not significantly differ between rural and urban groups: respectively, 8.16 ± 1.10 and 8.31 ± 1.29 h. Overweight/obesity percentage was 38.1% for rural and 31.7% for urban adolescents., Conclusions: Although traditional foods, including protective food, are still part of the adolescents' diet, low consumption of the energy food group and high consumption of processed food occurs regardless of location. As poor eating habits and insufficient sleep may contribute to overweight/obesity, educational nutrition programs should target these lifestyle variables.

Background: V/Q SPECT/CT is attractive for regional lung function assessment, but accurate delineation and quantification of functional lung volumes remains a challenge. Physiological intra and inter patient non-uniformity of V/Q SPECT images make conventional delineation methods of functional lung volumes inaccurate. In that context it would be of interest to build statistical maps of normal V/Q SPECT to assess the physiological variability of radiotracers. The aim of this study was to generate normal mean and standard deviation maps of regional lung function as assessed with V/Q SPECT/CT, with (AC) and without (NoAC) attenuation correction. Methods: During a 13 month period, 73 consecutive patients referred for suspected acute pulmonary embolism, that had normal V/Q SPECT/CT based on the interpretation of 2 independent nuclear medicine physicians, were selected. Four set of images were reconstructed: perfusion and ventilation images, AC, and NoAC, respectively. Statistical maps were created as follows: all cases were registered to a reference scan using the CT data, first with a rigid then with a non-rigid method. SPECTs reconstructions were then co-registered and normalized, and mean and standard deviation voxel-wise maps were calculated. To assess the consistency of generated maps to lung physiology and the potential impact of non-rigid registration, visual analysis and quantitative comparison with non-registered data were performed in the whole series. Quantitative comparison was also conducted in two randomly sampled independent subsets. Results: Perfusion mean maps showed a continuous negative posterior to anterior gradient, majored on the AC mean map. Perfusion standard deviation maps showed higher variability in the periphery of the lungs, but especially in the posterior areas. The ventilation mean map showed a slightly positive posterior to anterior gradient on NoAC mean ventilation map, while the AC mean map showed no gradient. The NoAC ventilation SD map showed a higher variability in the periphery of the lungs as compared with AC SD map. No statistical difference in the posterior to anterior gradient measurements was found between the generated mean statistical maps and the non-registered data, either in the whole series or across the two independent datasets. Conclusion: We proposed a methodology to create statistical normal maps for V/Q SPECTs. Maps were consistent with the known physiological non-uniformity and showed the impact of attenuation correction on the posterior to anterior gradient. These maps could be used for a Z-score analysis, and a better segmentation of healthy uptake areas., (Copyright © 2020 Bourhis, Robin, Essayan, Abgral, Querellou, Tromeur, Salaun and Le Roux.)

Background: Contributions from the cognitive neurosciences encourage the development of innovative tools in learning. Through an innovative intervention program called NeuroStratE, we conducted a study to analyze the impact of brain knowledge, with metacognitive approach, on the academic performance of students. This analysis concerns a cohort of 311 students aged 16. Students' school results were collected over one year and compared with those of a control group. These results are qualitatively refined with student feedback on the value of the intervention program, along with individual teacher interviews. This study showed no significant difference in school results between the two groups of students. However, the study shows the relevance of the program and students acquired knowledge about the brain's functioning. Moreover, this intervention highlights the evidence of the emergence in students of greater autonomy and better self-knowledge, both contributing to a feeling of self-efficacy, which is at the core of educational success., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/P SPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/P SPECT an essential method for the diagnosis of PE. When V/P SPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/P SPECT interpretation are discussed. In conclusion, V/P SPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.

Background:  We aimed to identify risk factors for residual pulmonary vascular obstruction after a first unprovoked pulmonary embolism (PE)., Methods:  Analyses were based on data from the double-blind randomized "PADIS-PE" trial that included 371 patients with a first unprovoked PE initially treated during 6 uninterrupted months; all patients underwent baseline ventilation-perfusion lung scanning at inclusion (i.e., after 6 months of anticoagulation). Each patient's pulmonary vascular obstruction indexes (PVOIs) at PE diagnosis and at inclusion were centrally assessed., Results:  Among the 371 included patients, residual PVOI was available in 356 patients, and 150 (42.1%) patients had PVOI ≥ 5%. At multivariable analysis, age > 65 years (odds ratio [OR], 2.81, 95% confidence interval [CI], 1.58-5.00), PVOI ≥ 25% at PE diagnosis (OR, 3.53, 95% CI, 1.94-6.41), elevated factor VIII (OR, 3.89, 95% CI, 1.41-10.8), and chronic respiratory disease (OR, 2.18, 95% CI, 1.11-4.26) were independent predictors for residual PVOI ≥ 5%. Patients with ≥ 1 of these factors represented 94.5% (123 patients) of all patients with residual PVOI ≥ 5%., Conclusion:  Six months after a first unprovoked PE, age > 65 years, PVOI ≥ 25% at PE diagnosis, elevated factor VIII, or chronic respiratory disease were found to be independent predictors for residual pulmonary vascular obstruction., Clinical Trials Registration:  URL: http://www.controlled-trials.com. Unique identifier: NCT00740883., Competing Interests: F.C. reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, and Astra Zeneca, and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Boehringer Ingelheim, Leo Pharma, Intermune, and Actelion. L.R. declares she has no conflict of interest related to this research. P.R. declares he has no conflict of interest related to this research. R.L.-M. declares he has no conflict of interest related to this research. E.P. declares she has no conflict of interest related to this research. C.T. declares she has no conflict of interest related to this research. O.S. reports having received research grant support from Bayer, Daiichi Sankyo, and Portola Pharmaceuticals, and fees or nonfinancial support for consultancy activities from Actelion, GlaxoSmithKline, Boehringer Ingelheim, and Chiesi. G.P. declares he has no conflict of interest related to this research. L.B. declares he has no conflict of interest related to this research. C.A.L. declares she has no conflict of interest related to this research. P.J. reports having received personal fees or nonfinancial support from Sanofi, GlaxoSmithKline, Bayer, Boehringer Ingelheim, and Leo Pharma. A.M. declares she has no conflict of interest related to this research. F.L. declares he has no conflict of interest related to this research. P.-Y.L.R. declares he has no conflict of interest related to this research. P.-Y.S. declares he has no conflict of interest related to this research. M.N. declares he has no conflict of interest related to this research. B.P. declares he has no conflict of interest related to this research. P.G. reports having received personal fees and nonfinancial support from Bayer and Leo Pharma. K.L. reports having received personal fees from Bayer-Health Care, Bristol-Myers Squibb, and Boehringer Ingelheim. S.M. declares she has no conflict of interest related to this research. P.M. reports having received research grants from Bayer, fees for board memberships from Bayer, Bristol-Myers Squibb/Pfizer, and Daiichi Sankyo, for lectures from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, and Sanofi, and for development of educational presentations from Bayer and Bristol-Myers Squibb/Pfizer. S.L. reports having received research grant support from Bayer and Sanofi, and fees for board memberships or consultancy from Bayer, Boehringer Ingelheim, Leo Pharma, and Sanofi. G.M. reports having received research grant support from Bayer, Boehringer Ingelheim, Leo Pharma, and Sanofi, having been an uncompensated board member and a consultant for Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Leo Pharma, and Pfizer, and having received travel support from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Leo Pharma, and Sanofi. C.L. reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Daiichi Sankyo, Leo Pharma, Intermune, and Actelion. No other potential conflict of interest relevant to this article was reported., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: This pilot study assessed the independent and incremental value of 68 Ga-V/Q PET/CT as compared with CT pulmonary angiography (CTPA) for the management of cancer patients with suspected acute pulmonary embolism (PE)., Methods: All 24 cancer patients with suspected acute PE prospectively recruited underwent both 68 Ga-V/Q PET/CT and CTPA within 24 h. PET/CT was acquired after inhalation of Galligas prepared using a Technegas generator and administration of 68 Ga-macroaggregated albumin. Initially, PET/CT and CTPA scans were read independently with the reader blinded to the results of the other imaging study. CTPA and PET/CT were then coregistered and reviewed by consensus between a radiologist and nuclear medicine physician. The therapeutic management was established by the managing physician based on all available data., Results: The diagnostic conclusion was concordantly negative in 18 patients (75%). Of the six discordant diagnoses on independent reading, combined interpretation of V/Q PET/CTPA enabled a consensus conclusion in two patients, excluding PE in one and confirming PE in the other, similar to the initial diagnostic conclusion of the V/Q PET/CT. Of the remaining four patients, three had a single subsegmental thrombus on CTPA but a negative V/Q PET/CT scan, and two of these did not receive long-term anticoagulation and did not have a venous thromboembolic event during a 3-year follow-up period. The third patient, along with a patient with a positive V/Q PET/CT scan but a negative CTPA scan, presented with acute complications preventing any conclusions with regard to the appropriateness of the V/Q PET/CT results in the management of PE. Overall, V/Q PET had an impact on management in four patients (17%)., Conclusion: In this pilot study, we demonstrated the feasibility and potential utility of V/Q PET/CT for the management of patients with suspected PE. V/Q PET/CT may be of particular relevance in patients with equivocal findings or isolated subsegmental findings on CTPA, adding further discriminatory information to allow important decision-making regarding the use or withholding of anticoagulation. Given the other advantages of V/Q PET/CT (reduced acquisition time, low radiation dose), and with the increasing availability of 68 Ga generators, PET/CT is a potential replacement for V/Q SPECT/CT imaging.

Objective: Following the implementation of single-photon emission computed tomography ventilation/perfusion (SPECT V/Q) in our department, we previously carried out an observational study over the period 2011-2013 that showed the safety of SPECT V/Q to rule out pulmonary embolism (PE). However, PE prevalence (28%) was high compared with some studies. Our hypothesis was that the use of SPECT V/Q may be responsible for an overdiagnosis of PE, especially at the implementation phase of the test. The aim was to carry out a time trend analysis of the evolution over the years of PE diagnosis with SPECT V/Q., Patients and Methods: To evaluate the time trend of SPECT V/Q results, the conclusions of all SPECT V/Q scans performed for a suspected acute PE in our department from April 2011 to December 2016 were collected. To confirm the safety of a diagnostic management on the basis of SPECT V/Q to rule out PE, a retrospective observational study of the outcome of patients assessed with SPECT V/Q for suspected acute PE was carried out during the period 2014-2016. SPECT V/Q was interpreted using a diagnostic cutoff of one segmental or two subsegmental mismatches. The final diagnostic conclusion was established by the physician responsible for patient care. The safety of SPECT V/Q was assessed by monitoring the risk of thromboembolic events during the 3-month follow-up period in patients left untreated on the basis of a negative SPECT V/Q., Results: Over the period 2011-2016, an average 16% (95% confidence interval: 10-22%) annual reduction in the proportion of positive SPECT V/Q results was observed. The percentage of positive SPECT V/Q results was 25.3% over the period 2011-2013 compared with 16.3% in 2014-2016 (P<0.0001). Out of the 696 patients analyzed over the period 2014-2016, the SPECT V/Q was positive, indeterminate, and negative in 118, 3, and 575 patients, respectively. The 3-month thromboembolic risk in patients in whom PE was deemed absent according to the SPECT V/Q was 3/543=0.55% (95% confidence interval 0.19-1.61)., Conclusion: A continuous decrease in the annual proportion of positive SPECT V/Q results was mainly observed while maintaining the safety of the test to rule out PE. Explanatory factors include the introduction of a combined SPECT/CT scan, increased experience and familiarity with the test, and an increased awareness of the risks and consequences of overdiagnosing PE.

Introduction: VTE-BLEED is a validated score for identification of patients at increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE). It is unknown whether VTE-BLEED high-risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score., Methods: This was a post hoc analysis of the randomized, double-blind, placebo-controlled PADIS-PE trial that randomized patients with a first unprovoked pulmonary embolism (PE) initially treated during 6 months to receive an additional 18-month of warfarin vs. placebo. The primary outcome of this analysis was recurrent VTE during 2-year follow-up after anticoagulant discontinuation, that is, after the initial 6-month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted for study treatment allocation, was compared between patients in the high- vs. low-risk VTE-BLEED group., Results: In complete case analysis (n = 308; 82.4% of total population), 89 (28.9%) patients were classified as high risk; 44 VTE events occurred after anticoagulant discontinuation during 668 patient-years. The cumulative incidence of recurrent VTE was 16.4% (95% confidence interval [CI], 10.0%-26.1%; 14 events) and 14.6% (95% CI, 10.4%-20.3%; 30 events) in the high-risk and low-risk VTE-BLEED groups, respectively, for an adjusted hazard ratio of 1.16 (95% CI, 0.62-2.19)., Conclusion: In this study, patients with unprovoked PE classified at high risk of major bleeding by VTE-BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.

Accuracy studies are the cornerstone of the evaluation of new diagnostic tests. In an accuracy study, patients with a clinical suspicion of disease undergo both the new tests that is being evaluated, and the reference test or "gold-standard" test for the disease. Patients are stratified according to the test result and to whether or not the diagnosis was confirmed by the reference test. Main accuracy indices include the sensitivity (proportion of patients who test positive among those who have the disease), specificity (proportion of patients who test negative among those without the disease), as well as the positive and negative predictive values (proportion of patients with the disease among those with a positive test, and of patients without the disease among those with a negative test, respectively). In appraising an accuracy study, the reader should check that the study design and analysis follow methodological standards. The study population should be representative of the population in which the test will be used in practice. The new test should be interpreted in a blinded and independent fashion from the reference standard to avoid expectation bias, and should not be used to establish the diagnosis (incorporation bias). The reproducibility should be verified. Interpretation criteria and technical aspects should be described with enough details to allow replication. Provided that these conditions are met, the next step is to decide whether the test may be used for patient care. The clinical setting in which the test will be used, and the corresponding pretest probability of disease, will determine how best can the test be used in practice., (Copyright © 2018. Published by Elsevier Inc.)

Differences between computed tomography pulmonary angiography and ventilation-perfusion lung scanning in pregnant patients with suspected acute pulmonary embolism are not well-known, leading to ongoing debate on which test to choose. We searched in PubMed, EMBASE, Web of Science and the Cochrane Library databases and identified all relevant articles and abstracts published up to October 1, 2017. We assessed diagnostic efficiency, frequency of non-diagnostic results and maternal and fetal exposure to radiation exposure. We included 13 studies for the diagnostic efficiency analysis, 30 for the analysis of non-diagnostic results and 22 for the radiation exposure analysis. The pooled rate of false negative test results was 0% for both imaging strategies with overlapping confidence intervals. The pooled rates of non-diagnostic results with computed tomography pulmonary angiography and ventilation-perfusion lung scans were 12% (95% confidence interval: 8-17) and 14% (95% confidence interval: 10-18), respectively. Reported maternal and fetal radiation exposure doses were well below the safety threshold, but could not be compared between the two diagnostic methods given the lack of high quality data. Both imaging tests seem equally safe to rule out pulmonary embolism in pregnancy. We found no significant differences in efficiency and radiation exposures between computed tomography pulmonary angiography and ventilation-perfusion lung scanning although direct comparisons were not possible., (Copyright© 2019 Ferrata Storti Foundation.)

Ventilation/Perfusion (V/Q) positron emission tomography computed tomography (PET/CT) is now possible by substituting Technetium-99m ( 99m Tc) with Gallium-68 ( 68 Ga), using the same carrier molecules as conventional V/Q imaging. Ventilation imaging can be performed with 68 Ga-carbon nanoparticles using the same synthesis device as Technegas. Perfusion imaging can be performed with 68 Ga-macroaggregated albumin. Similar physiological processes can therefore be evaluated by either V/Q SPECT/CT or PET/CT. However, V/Q PET/CT is inherently a superior technology for image acquisition, with higher sensitivity, higher spatial and temporal resolution, and superior quantitative capability, allowing more accurate delineation and quantification of regional lung function. Additional advantages include reduced acquisition time, respiratory-gated acquisition, and a lower impact on human resources. V/Q PET imaging offers an opportunity to improve the accuracy and utility of V/Q imaging in various pulmonary conditions. For pulmonary embolism, V/Q PET/CT scan may improve the diagnostic performance of the test owing to a better characterization of the pattern of defects and allow an accurate quantification of the extent of vascular obstruction. Establishing an accurate functional map of the regional ventilation and perfusion in the lungs may be relevant in many other clinical situations, including preoperative assessment of the lung cancer patients, radiotherapy planning, or presurgical evaluation of patients undergoing lung volume reduction surgery., (Copyright © 2018. Published by Elsevier Inc.)

Background: In patients with a first, unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulant therapy (AT) is controversial due to tightly balanced risks and benefits of indefinite anticoagulation. The objective of this study is to assess among patients with a first acute pulmonary embolism (PE) who received ≥3 months of AT and thereafter had a planar lung scan, whether residual pulmonary vascular obstruction (RPVO) is associated with VTE recurrence after discontinuation of AT., Methods and Analysis: We will conduct a systematic review with a meta-analysis of individual participant data of contemporary studies evaluating the prognostic significance of RPVO in patients with a first acute PE. We will search from inception to 24 January 2018, PubMed, Medline, Embase and Cochrane's Central Registry for Randomized Controlled Trials, CENTRAL for randomized controlled trials and prospective cohort studies. Two reviewers will conduct all screening and data collection independently. The methodological quality and risk of bias of eligible studies will be carefully and rigorously assessed using the Risk Of Bias In Non-randomised Studies of Interventions tool. The primary objective will be to assess the relationship between RPVO on ventilation-perfusion scan after completion of at least 3 months of AT after an acute PE event, and the risk of an objectively confirmed symptomatic recurrent VTE (including deep vein thrombosis or PE) or death due to PE. The secondary objectives will include the assessment of the optimal RPVO cut-off and the risk of recurrent VTE, as well as the relationship between the relative change in RPVO between PE diagnosis and at discontinuation of AT (≥3 months) and risk of recurrent VTE., Ethics and Dissemination: This study of secondary data does not require ethics approval. It will be presented internationally and published in the peer-reviewed literature., Prospero Registration Number: CRD42017081080., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an undiagnosed cancer. We assessed the cost-effectiveness of 18 F-Fluorodesoxyglucose Positron Emission/Computed Tomography (FDG PET/CT) plus limited screening and limited screening strategies in patients with unprovoked VTE from the perspectives of the Ontario (Canada) and French health care systems., Methods: We conducted a cost-effectiveness analysis based on a published randomized controlled trial of 394 patients aged 18 years or older who were diagnosed with unprovoked VTE. We obtained data with respect to efficacy and health care utilization from the published trial. The primary measure of effectiveness was the number of avoided cases of delayed cancer diagnosis and the secondary measure of effectiveness was the quality adjusted life year (QALY) at the end of the study in each group. We used generalized linear models to estimate incremental cost-effectiveness ratios (ICER) while controlling for patient demographic and clinical characteristics. Results were presented as the incremental cost to avoid one case of delayed cancer diagnosis and the incremental cost per QALY gained. The 95% confidence intervals (CIs) were estimated using bootstrap re-sampling procedures with 5000 iterations., Results: Compared to a limited screening strategy, the ICER of limited strategy plus FDG PET/CT scan was C$ 26,840.19 (95% CI: C$ 24,046.51; C$ 34,581.53) per one avoided case of delayed cancer diagnosis from the Ontario health system perspective and €16,370.45 (95% CI: € 9904.48; € 39,578.91) per one avoided case of delayed cancer diagnosis from the French health system perspective. The probabilities that addition of FDG PET/CT to limited screening is cost-effective rose with increasing willingness to pay values. Compared with the limited screening, the extensive screening was associated with C$ 3412.85 per QALY gained (95% CI: 1463.89; -13,935.88) from the Ontario health system perspective and €2162.83 per QALY gained (95% CI 958.78; -10,544.42) from the French health system perspective., Conclusion: Addition of a FDG PET/CT for occult cancer diagnosis was associated with better health outcomes (fewer cases of delayed cancer diagnosis and greater QALYs) and a higher cost from the perspective of publicly funded health care systems; the cost-effectiveness results are however highly uncertain., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Rationale: Ventilation/perfusion (V/Q) single-photon-emission computed tomography (SPECT) has arisen as an alternative to computed tomography pulmonary angiography (CTPA) in patients with pulmonary embolism (PE) suspicion. The addition of low dose CT (ldCT) to V/Q SPECT improves the specificity of the test, allowing for potential alternative diagnosis., Patient Concerns and Diagnosis: Here we presented a case of an aortic intramural hematoma (IMH) diagnosed on the ldCT portion of V/Q SPECT combined with CT. A 74-year-old man suffering from sudden-onset chest pain was referred to our nuclear medicine department for PE suspicion., Intervention and Outcome: A V/Q SPECT combined with nonenhanced ldCT ruled out PE diagnosis. Nevertheless, ldCT revealed high attenuation aortic wall thickening suggestive of aortic IMH. Chest CT angiography showed mild dilatation and circumferential thickening of aortic wall confirming Stanford type A IMH involving the entire ascending aorta., Lesson: This case illustrates the potential usefulness of combining ldCT to V/Q SPECT in providing alternative diagnosis in suspected PE patients.